tbuckley/cabot-search huggingface dataset:
Education modalities for serious illness communication training: A scoping review on the impact on clinician behavior and patient outcomes.
Authors: Melissa Lavecchia, Jeffrey Myers, Daryl Bainbridge, Nadia Incardona, Oren Hannun Levine, Leah Steinberg, Daniel Schep, Joanna Vautour, Shilpa Jyothi Kumar, Hsien Seow
Journal: Journal of Clinical Oncology (2023)

e24003 Background: Several clinician training interventions that address serious illness communication have been developed over the past decade. While numerous studies report the impact on clinician attitude, confidence and intention to change practice, less is reported on individual education modalities and their impact on actual behavior change and patient outcomes. This study's aim was to examine what is known about the education modalities used in serious illness communication training and their impact on clinician behaviors and patient outcomes. Methods: A scoping review using the Joanna Briggs Methods Manual for Scoping Reviews was conducted of studies that specifically measured clinician behaviors or patient outcomes. Ovid MEDLINE and EMBASE databases were searched for English-language studies published between January 2011, and November 2021. Results: The search identified 1132 articles: 60 met inclusion criteria describing 49 unique interventions. Common education modalities used were a single workshop (n = 18), multiple workshops (n = 8), single workshop with coaching (n = 7), multiple workshops with coaching (n = 5); though they were inconsistently structured. Studies reporting improved clinician skills tended to be in simulation settings with neither clinical practice nor patient outcomes explored. While studies reporting behavior changes or improved patient outcomes did not confirm improvements in skills. As multiple modalities were commonly used and often embedded within larger quality improvement initiatives, the impact of individual modalities could not be determined. Conclusions: To advance the evidence of the benefits of serious illness communication training, well-defined education modalities and consistent outcome measures for behavior change and patient outcomes are needed.
Rates of potentially actionable germline variants in homologous recombination repair genes in a large international cohort outside of the United States.
Authors: Sarah M. Nielsen, Brandie Heald, Joanne YY Ngeow, Yanin Chavarri Guerra, Emily M. Russell, Edward D. Esplin, Daniel Esteban Pineda Alvarez
Journal: Journal of Clinical Oncology (2023)

10590 Background: Identification of pathogenic germline variants (PGVs) in homologous recombination repair (HRR) genes among patients (pts) with breast (BC), ovarian (OC), pancreatic (PaC), and prostate cancer (PrC) is critical to determine potential eligibility for targeted therapies such as PARP inhibitors (PARPi). It is important to evaluate the frequency and patterns of PGVs across different regions of the World to help inform the counseling of pts and implementation of precision medicine. Methods: A retrospective analysis of pts with BC, OC, PaC, and/or PrC cancer undergoing GGT through a single laboratory was conducted. The location of the ordering provider determined the assigned region, which included: Asia-Pacific (APAC), Latin America (LATAM), Middle East and African (MEA), and United Kingdom and Europe (UKEU). Analyses were limited to pts tested for PARPi-eligible (in the US) HRR genes and PGV analysis to the 10 most frequent genes for that cancer type. Descriptive statistics and Chi square with Yates correction were utilized. Significance was set at p&lt;0.05. Results: The cohort consisted of 40,539 pts with an average age at testing of 51 years, the majority of whom had BC (81%) (Table). The median number of genes tested ranged from 14-85 (Table). BRCA1 and BRCA2 were the most frequent genes with PGVs (3,358 pts, 8%). LATAM BC pts had significantly higher rates of BRCA1/2 PGVs (10%) than the other 3 regions ( p &lt;0.0007). OC BRCA1/2 rates were high, and statistically similar, across regions (15-17%, p&gt;0.08). Rates of BRCA1/2 and PALB2 in PaC pts did not differ between regions (4-7%, p&gt;0.08), nor did rates of BRCA1/2, CHEK2, ATM, and PALB2 in PrC pts (7-11%, p&gt;0.16) (Table). In sum, 3,434 pts (9% of those tested for the eligible genes) had PGVs in the above PARPi-eligible HRR genes. A notable limitation is that pts were ascertained by cancer type but information on other PARPi eligibility, namely metastatic/advanced disease, was not available. Conclusions: 1 in 12 pts were found to carry PARPi-eligible PGVs across the 4 cancer types and regions analyzed. Knowledge of these PGVs can help inform public health policies, current and future treatment strategies, and identify at-risk family members. In some countries, GGT may represent a more cost-effective and accessible pathway to targeted therapies compared to tumor profiling due to ease of sample collection and lower cost of testing. [Table: see text]
Surgical outcomes of patients with resectable non-small-cell lung cancer receiving neoadjuvant immunotherapy with nivolumab plus relatlimab or nivolumab: Findings from the prospective, randomized, multicentric phase II study NEOpredict-Lung.
Authors: Clemens Aigner, Bert Du Pont, Koen Hartemink, Marcel Wiesweg, Michel Vanbockrijck, Kaid Darwiche, Balazs Hegedus, Alexander Schramm, Hubertus Hautzel, Brigitte Maes, Dirk Theegarten, Hans-Ulrich Schildhaus, Paul Baas, Kristof Cuppens, Martin H. Schuler, Till Plönes
Journal: Journal of Clinical Oncology (2023)

8500 Background: Feasibility of surgical resection for non-small-cell lung cancer (NSCLC) after preoperative immune checkpoint inhibitor therapy (PICIT) with PD-1/PD-L1 and CTLA-4 inhibitors has been established. This study reports the first data on surgery after preoperative LAG-3 inhibition in NSCLC patients. Methods: Patients with histologically confirmed NSCLC stage IB, II or IIIA (UICC 8th edition) were randomized to receive two preoperative doses (q14d) of nivolumab (240 mg, arm A), or nivolumab (240 mg) plus relatlimab (80 mg, arm B). Primary study endpoint was the number of patients undergoing curatively intended surgery within 43 days of initiation of PICIT. Surgery was performed following the institutional standards. Outcomes and perioperative events were prospectively recorded. Results: 60 patients (29 female) were randomized 1:1 from 4/2020 to 7/2022. All patients were operated within 43 days after initiation of PICIT. Median age in arm A was 65 (43-78) years and 67 (44-81) years in arm B. Clinical UICC stages were similar between both arms. Central tumor location was present in 50% in arm A and 45% in arm B. R0 resection was achieved in 57 patients (95% ITT population, 98,3% curatively resected population). Two patients had pleural carcinosis only detected at surgery, and 1 patient had R1 resection. Resection was performed by lobectomy (n=23 and 24), bilobectomy (2 and 1), sleeve lobectomy (5 and 4) and combined lobectomy+segmentectomy (0 and 1). Surgical approach was either by videothoracoscopy (n=60% and 63,3%) or thoracotomy (n=40% and 36,6%). Conversion was required in 3 vs. 2 patients. Median operation time was 149 (77-234) and 165 (61-205) minutes. Median number of resected lymph nodes was 15 (3-52) and 10 (3-50). Intraoperative bleeding from the pulmonary artery was observed in 1 patient in each arm and was managed without sequelae. Postoperative complications occurred in 33,3% and 26,6%. Median hospital stay was 7 (2-22) and 5,5 (2-24) days. Complete or major histopathological response was observed in 27% and 30%. Overall perioperative 30-day mortality was 0%. No negative impact on adjuvant therapy was observed. The 12 months OS rate across both arms was 96% (95% Cl: 83-99%), the DFS rate was 91 % (78-97%). Conclusions: Curative surgical resection following neoadjuvant combined PD-1/LAG-3 inhibition was equally safe and feasible as after PD-1 inhibition alone. Perioperative course, complications rate and outcome are comparable to other neoadjuvant regimens. Standard adjuvant therapies can be safely administered in this setting. Clinical trial information: NCT04205552 .
Estimated life-years gained and resultant cost savings from follow-up colonoscopy after a positive multi-target stool DNA (mt-sDNA) test for colorectal cancer screening in commercially insured and Medicare populations.
Authors: A. Mark Fendrick, John B. Kisiel, Derek W. Ebner, Vahab Vahdat, A. Burak Ozbay, Chris Estes, Paul J. Limburg
Journal: Journal of Clinical Oncology (2023)

6642 Background: Although follow up colonoscopy (COL) after a positive stool-based colorectal cancer (CRC) screening test is necessary to complete the CRC screening process, follow-up COL rates remain suboptimal, especially among underserved populations. As of January 2023, federal policies require commercial insurers and Medicare to eliminate out of pocket costs for follow-up COL. To estimate the implications of this policy change, we compared the clinical and fiscal outcomes for a simulated cohort receiving a follow-up COL after a non-invasive CRC test ($0 cost sharing), compared to the same cohort not completing follow-up COL (status quo). Methods: Using the validated CRC-AIM model, we simulated a cohort of 6 million average-risk individuals who received mt-sDNA (commercial patients at age 45 and Medicare patients at age 65) and further analyzed only the population with positive mt-sDNA. Life-years gained, CRC incidence, CRC-related mortality and total costs of care (inclusive of CRC screening and treatment) were calculated for a cohort that underwent follow-up COL and compared these outcomes to that same cohort that did not complete follow-up COL. The cost of follow-up COL was assumed to be $1,576 for Medicare and $3,086 for commercially insured patients ($0 out of pocket costs for all). Results: Patients undergoing follow-up COL after a positive mt-sDNA experienced more life-years (83 per 1,000 commercially insured patients and 80 per 1,000 Medicare beneficiaries) compared to those who did not undergo follow-up COL. The follow-up COL resulted in reductions in CRC incidence and CRC mortality by 14% and 16% for commercial and 19% and 23% for Medicare beneficiaries, respectively. Compared to those patients with a mt-sDNA positive test result and did not complete follow-up COL, the total cost per patient for those receiving follow-up COL was $3,339 less for commercially insured ($15,690 – no follow up vs. $12,351 – follow up) and $4,382 less for Medicare beneficiaries ($19,337 – no follow up vs. $14,955 – follow up). Total spending for patients receiving follow-up COL was cost-saving when compared to no follow-up as long as the COL costs were less than $6,269 for commercial plans and $5,753 for Medicare. Conclusions: Completing a follow-up COL after a positive mt-sDNA screening saves lives, enhances equity, and lowers total expenditures. Thus, health care stakeholders should invest in efforts to identify and reduce barriers that ultimately lead to an increase uptake of this potentially lifesaving and cost-reducing intervention.
Short-term locally advanced gastric cancer management: A cost-effectiveness analysis.
Authors: Vishnu Prasath, Patrick L. Quinn, Simran Arjani, Sharon Li, Joseph B. Oliver, Omar Mee Mahmoud, Mohammed Jaloudi, Kaveh Hajifathalian, Ravi Chokshi
Journal: Journal of Clinical Oncology (2023)

e16065 Background: Across the nation, patients with locally advanced gastric cancer (LAGC) are managed with modalities including upfront surgery (US), neoadjuvant chemoradiation therapy (NCRT), and perioperative chemotherapy (PCT). Treatment modalities themselves are associated with adverse effects which can lead to difficulty with treatment adherence in the short-term. As preoperative therapies have demonstrated survival benefits over US, long-term outcomes are expected to vary, but it is not known if differences in adherence impacts short-term treatment outcomes. We sought to perform a decision analysis comparing costs and quality-of-life associated with short-term outcomes in the treatment of patients with LAGC to identify the most cost-effective option. Methods: We designed a decision tree model to investigate the survival and costs associated with the three utilized management modalities for T2 or higher gastric cancer in the United States: US, PCT, and NCRT. The tree described costs and treatment strategies over a six-month time horizon to incorporate the complete treatment regimen and various treatment failure points encountered during therapy. Costs were derived from 2022 Medicare reimbursement rates using the third-party payer perspective for physicians and hospitals. Effectiveness was represented using quality-adjusted life months (QALMs). One QALM equates to one month of perfect health, while zero QALMs is equivalent to death. One-way, two-way, and probabilistic sensitivity analyses were utilized to test the robustness of our findings. Results: PCT was the most cost-effective treatment modality for LAGC over US and NCRT with a cost of $40,792.16 with 4.14 QALMs. US had a cost of $55,575.57 with 4.20 QALMs. NCRT was dominated by the other options with a cost of $56,510.64 with 3.70 QALMs. Across 100,000 Monte-Carlo simulations, 55.2% of trials favored PCT and the remainder favored US (44.8%). NCRT was not favored in the probabilistic sensitivity analysis. Finally, one-way and two-way sensitivity analyses did not identify any situations where alternative treatment modalities were preferred over PCT. Conclusions: In our simulated patients with diagnosed gastric cancer, the most cost-effective treatment strategy was PCT. This further confirms the preference of this modality over others in LAGC. While US demonstrated improved QALMs over PCT, the associated cost was too great to justify the benefits. [Table: see text]
Perioperative safety and outcomes following radical prostatectomy in setting of locally advanced, node positive, and metastatic prostate cancer.
Authors: Kerith Ruoyao Wang, Rishabh Simhal, Yash Shah, James Ryan Mark, Mihir S Shah, Leonard G. Gomella, Costas D. Lallas, Thenappan Chandrasekar
Journal: Journal of Clinical Oncology (2023)

e17108 Background: Historically, definitive surgical management with radical prostatectomy (RP) has only been considered an option for the treatment of localized prostate cancer (PCa). However, recent data may suggest a role for RP in advanced PCa treatment. Currently, there is limited data on the safety and perioperative outcomes of RP in this setting. Here, we aim to compare the perioperative outcomes of RP for locally advanced, node positive, and metastatic PCa using the American College of Surgeons National Surgical Quality Improvement Project (NSQIP) new procedure targeted database. Methods: RP procedures performed between 2019-2020 were identified. Patients were stratified to compare the effect of locally advanced disease (T3-4), node-positivity (N+), and metastasis (M+) against patients with localized (T1-2 N0 M0) PCa. Baseline demographics and 30-day outcomes, including operative time, hospital length-of-stay, 30-day mortality, readmissions, reoperations, major complications, minor complications, and surgery-specific complications, were compared between groups. Results: Pathologic staging data was available for 9,276 RPs. Baseline demographics were comparable. There was a slightly higher rate of minor-complications in the locally-advanced cohort, but no significant difference in major-complications, 30-day-mortality, readmissions, or rectal injuries. In comparison, while node-positivity was associated with longer operative time, LOS, and incidence of 30-day renal failure, it was not associated with a higher rate of any major, minor or surgery-specific complication. Similarly, RP for metastatic cases appeared to be comparably safe to those with M0 disease, although they were associated with a slightly higher rate of bleeding, prolonged-NG-tube use, and ureteral obstruction. Conclusions: RP for patients with locally advanced, node positive, and metastatic prostate cancer appears to be safe, and is not associated with significantly higher rates of 30-day mortality or major complications compared to localized prostate cancer. Given the previously demonstrated survival benefit in treating the primary tumor in advanced disease with radiation therapy, there may be a role for the RP in treating advanced PCa. Further studies are needed to better characterize the risks and benefits of surgery in these patients.
Tolerability of lutetium-177–PSMA-617 in men with prostate cancer and baseline cytopenia.
Authors: Ahmad S Abdelrazek, Ahmed Mahmoud, Geoffrey Johnson, Derek R Johnson, Corrie R Bach, Jacob Orme, Rodrigues Pessoa Rodrigo, Reza Nabavizadeh, Matthew Thorpe, Eugene D. Kwon, Ayse T. Kendi, Daniel S Childs
Journal: Journal of Clinical Oncology (2023)

e17057 Background: Results from the VISION trial (NCT03511664) led to the approval of lutetium-177 (177Lu)–PSMA-617 for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This trial excluded patients with baseline cytopenias, thus safety in this frequently encountered patient population is unknown. We aimed to use real-world data to describe the tolerability of radioligand therapy in those with poorer bone marrow reserve. Methods: We retrospectively reviewed the records of all patients, who received a first dose of 177Lu–PSMA-617 at Mayo Clinic in the interval of April 26, 2022, to December 1, 2022. Patients were categorized as having poor marrow reserve on the basis of pre-treatment hematologic parameters, including: (1) an anemia cohort with hemoglobin (Hg) less than 9 g/dL, (2) a thrombocytopenia cohort with platelets (Plt) less than 100 x 10 9 /L, (3) a leukopenia cohort with white blood cell count (WBC) less than 2.5 x 10 9 /L, and (4) a multiple cytopenia cohort. These were exclusionary parameters from the VISION trial. Longitudinal laboratory data and clinical outcomes were collected and analyzed using descriptive statistics. Results: At data cutoff, 185 patients had received one or more doses of 177Lu, including 26 (14%) with at least one baseline cytopenia prior to their first cycle of treatment. In total, there were 19 (73%) patients with anemia, 3 (12%) with thrombocytopenia, 2 (8%) with leukopenia, and 2 (8%) with multiple cytopenias at baseline. The median number of cycles received thus far is 3, including 14 (54%) who are still receiving therapy and 12 (46%) who have permanently discontinued treatment. Median longitudinal changes in blood counts for the anemia cohort are presented in Table 1. Reasons for treatment discontinuation include: toxicity (n = 2), disease progression (n = 5), death (n = 4), or other (n = 1). Dose reductions or treatment delays for worsening myelosuppression were utilized in 3 (12%) and 5 (19%) patients, respectively. Transfusions of packed red blood cells or platelets were required for 16 (62%) patients. A total of 6 (23%) received care in the emergency department or were hospitalized. Conclusions: Treatment discontinuation for toxicity was rare among men with mCRPC and baseline cytopenias, while receiving 177Lu; however, these patients have an overall poor prognosis. [Table: see text]
Pembrolizumab immunotherapy in advanced and recurrent/metastatic salivary gland carcinoma (R/M SGC): A systematic review and meta-analysis.
Authors: Victor Filogonio, Yara Rafaela Maia, Lucas Henrique Maia
Journal: Journal of Clinical Oncology (2023)

e18101 Background: Treatment options for advanced R/M SGC are a limited and with variable response rates due to their safety/toxicity profile and the heterogenous l histology. Recent clinical trials tested pembrolizumab (PMB), a PD-1 inhibitor, in diverse settings. Methods: We performed a systematic review and single arm meta-analysis of clinical trials of PMB monotherapy or combined therapy in advanced and R/M SGC. PubMed, Scopus, and Cochrane database were searched for clinical trials published up to January 31, 2023. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. The primary endpoints of interest were complete/partial response (CR,PR) and disease control (DC= SD or better response) per RECIST v1.1, at any period of the trial. Results: Out of 199 database results, 4 clinical trials and 180 patients were included, all were using some form of PMB therapy. Overall, PMB was associated with a CR,PR ratio of 5.6% (95% CI 0.01-0.10, I²=25%, p=0.262) and DC ratio of 58.4% (95% CI 0.50-0.66, I²=13%, p=0.326), somewhat similar to recent evidence of PD-1/CTLA-4 combined therapy (nivolumab + ipilimumab [CR,PR=6-16%) in ongoing phase II clinical trials or PD-1 monotherapy (nivolumab [CR,PR=6%; SD=50%] in a completed clinical trial. Other systemic therapies, in which the current guidelines are based, include TKI (lenvatinib + sorafenib PR=3-15%; SD=50-94%) for adenoid cystic carcinoma (ACC); NTRK (larotrectinib CR,PR=90%, entrectinib CR,PR=86%), HER2 (transtuzumab associations CR,PR=60-90%), and AR (leuprorelin + bicalutamide CR,PR=42%, enzalutamide PR=4-15%; SD=52%) in non-ACC; and cytotoxic chemotherapy associations CR,PR=16-34% in heterogeneous histology tumors. Conclusions: There are marked limitations to the applicability of these findings in clinical practice, therefore a cautionary approach to this data is recommended, given their overall low statistical power, heterogenous histology, and tolerability to adverse effects. New trials with better standardized outcomes and comparative arms for different therapy associations and populations will help clarify the effects PD-1 inhibitors in the treatment of advanced and R/M SGC. [Table: see text]